The technique for producing so-called nano-sized crystalline particles with respective sizes within a range of several nm to several hundred nm is developed so that nano-sized crystals for various materials can be produced in the state of monodispersity. Among them, when the inorganic particles made of metallic oxide are synthesized in an organic solvent, the inorganic particles which are finely controlled in particle size and are uniformed in particle diameter can be obtained under the state of monodispersity. Such fundamental researches and developments for nano-sized crystal are being intensely progressed and the thus obtained results are expected as the applications for various technical fields.
Non-patent Reference 1 (J. Am. Chem. Soc. 2004, 126, P. 273-279) has reported as one of applications the production process of nano-sized Fe3O4 particles. In the production process, ferric acetylacetonate complex salt is solved in a solvent mixed with oleic acid and 1,2-hexadecandic diol containing oleylamine and having high boiling point to obtain nano-sized Fe3O4 particles which are finely controlled in particle size and uniformed in particle diameter. Non-patent Reference 1 has also reported that cobalt and/or manganese acetylacetonate complex salt are contained in addition to the ferric acetylacetonate complex salt such that the iron (Fe) atoms of the nano-sized Fe3O4 particles are partially substituted with the cobalt atoms and/or the manganese atoms. According to these production processes, the intended nano-sized crystals can be finely controlled in particle size in an organic solvent. The well averaging in particle diameter is considered to be originated from that the corresponding nuclei are created simultaneously and the intended nano-size crystals are independently grown under almost the same condition as one another.
Non-patent Reference 2 (Nat. Mater. 2004, 3, P. 891-895) has reported that iron chloride and sodium oleate are reacted with one another to form iron oleate complex, which is solved in 1-octadecene containing oleic acid, increased slowly in temperature up to 320° C. and maintained at the same temperature for a predetermined period of time, thereby synthesizing a large amount of nano-sized crystalline Fe3O4 particles. The nano-sized crystalline Fe3O4 particles are covered with oleic acid and thus, dispersed well in a non-polar solvent such as hexane or toluene.
The nano-sized crystalline particles synthesized by using an organic solvent are nano-sized crystalline particles which are finely controlled in particle size and uniformed in particle diameter under the state of monodispersity. Therefore, the nano-sized crystalline particles are expected as the application for medical and/or biotechnology field as described in Patent Reference 1 (JP-A 10-503281 (KOHYO)), Patent Reference 2 (JP-A 2000-507197 (KOHYO)) and Patent Reference 3 (JP-A 2006-502572 (KOHYO)). The particles to be used in the medical and/or biotechnology field are normally used in the state of dispersion in a polar solvent such as a water. However, the nano-sized particles synthesized as described above can be dispersed well in a non-polar solvent, but not dispersed well in the polar solvent such as the water because the surfaces of the synthesized nano-sized particles are covered with aliphatic acid having long alkyl chain such as oleic acid.
As a method for substituting the aliphatic acid covering at the surfaces of the nano-sized particles with another surface covering suitable for the dispersion in the water, Non-patent Reference 1 discloses that aminoundecanoic acid tetramethylammonium as amphiphilic molecule is added and agitated in a hexane solvent where the hydrophobic Fe3O4 nano-sized particles covered with the oleic acid are dispersed so that the oleic acid is released from the surfaces of the Fe3O4 nano-sized particles, thereby producing hydrophilic Fe3O4 nano-sized particles.
In this way, in order to change the surface covering for the aliphatic acid-covering particles with a new covering by mixing and agitating the aliphatic acid-covering particles and a new surface covering material in a non-polar solvent, both conditions are required to be satisfied: One condition is that the new surface covering material can be solved in the non-polar solvent and the other condition is that the displacement reaction of the aliphatic acid surface covering by the new surface covering material can be conducted. In the case that the nano-sized particles are employed in the medical and/or biochemical field, the new surface covering material is required to be selected in view of the biocompatibility. In this point of view, even though the new surface covering material has the biocompatibility and thus, preferable for the substitution, the new surface covering material cannot be employed if the new surface covering material does not satisfy both of the conditions as described above. For example, it is very preferable that the nano-sized particles are covered with citric acid as disclosed in Patent Reference 4 (JP-A 2006-282582 (KOKAI)), but that the surface covering for the nano-sized particles formed according to Non-patent Reference 1 is substituted with the citric acid surface covering is not known.
Also, non-patent Reference 3 (J. Am. Chem. Soc. 2005, 127, p. 5732-5733) has reported that if the hydrophobic surface covering, which is formed through the thermal dissolution of iron acetylacetonato complex salt in an organic solvent, for the ferrite nano-sized particles is substituted with hydrophilic dimercaptosuccine acid surface covering, the intended hydrophilic surface covering ferrite nano-sized particles can be obtained which are suitable for the use in a living body. In non-patent Reference 3, the dimercaptosuccine acid is selected as a new surface covering material satisfying two conditions that the new surface covering material can be solved in the non-polar solvent and the displacement reaction of the aliphatic acid surface covering by the new surface covering material is conducted. As the result from that the aliphatic acid surface covering is practically substituted with the dimercaptosuccine acid surface covering, it was turned out that the dimercaptosuccine acid surface covering gradually solves the ferrite nano-sized particles. Namely, the nano-sized particles covered with dimercaptosuccine acid surface covering has a problem of chemical unstability.    Patent Reference 1: JP-A 10-503281 (KOHYO)    Patent Reference 2: JP-A 2000-507197 (KOHYO)    Patent Reference 3: JP-A 2006-502572 (KOHYO)    Patent Reference 4: JP-A 2006-282582 (KOKAI)    Non-patent Reference 1: J. Am. Chem. Soc. 2004, 126, p. 273-279    Non-patent Reference 2: Nat. Mater. 2004, 3, P. 891-895    Non-patent Reference 3: J. Am. Chem. Soc. 2005, 127, p. 5732-5733